Anorexia nervosa (AN) is a serious medical condition with a high rate of both mortality and chronicity. Affecting both men and women, the mortality rate for the condition is estimated at 10% to 15%, and an additional 10% to 15% will go on to develop a chronic form of the illness.1,2
Current treatments are able to help many individuals who suffer from this disorder. While there have been promising advances over the last decade in the treatment of adolescent AN through the development of novel forms of family therapy, there have been few significant improvements in treatment for adults, especially those with chronic illness. Treatments focused on this group would have a significant effect on reducing both mortality and general suffering experienced by these individuals.
Deep Brain Stimulation (DBS) is a neurosurgical procedure initially developed for the management of treatment-refractory movement disorders, such as Parkinson disease and essential tremor. More recently, there has been interest in investigating the use of the procedure in other circuit-based disorders, including psychiatric conditions, such as depression, OCD, schizophrenia, and Alzheimer dementia. Since 1987, over 100,000 individuals have had the procedure for neurological or psychiatric conditions, and the number of trials for new indications continues to grow.
During a DBS procedure, electrodes are introduced bilaterally under stereotactic and fluoroscopic guidance to deep brain targets identified on a pre-operative MRI. These electrodes are tested in the operating room with the patient awake and under local anesthesia, and then in a separate procedure the electrodes are connected to a programmable stimulator implanted in the anterior chest wall. The device is then activated a short period of time later, with the parameters of the stimulation monitored externally. The battery life for the stimulator depends on the intensity of the stimulation, but is typically 2 to 4 years. Replacements are performed with local anesthesia and sedation.
The rationale for the use of DBS in AN derives from several sources.3 The insula has been implicated in interoception—that is, in the way in which the body is experienced internally, and appears to be involved in decisions about acceptability of food. The anterior cingulated (AC), and in particular the subcallosal cingulate (SCC), appear to be implicated both structurally and functionally in the symptoms of AN. The AC is also involved in both mood states and the regulation of affect, both directly and through its influence on higher cortical structures. Finally, the ventral striatum, or nucleus accumbens (NAC), may be involved in reward circuits, with some research suggesting that the NAC does not function normally in anorexia nervosa patients compared with healthy controls. It was thus thought that stimulation of either the AC or NAC would be potential targets for a trial of DBS in AN.
In our research, we decided to focus our attention on the AC, and specifically the subcallosal cingulate. The rationale for this decision related to our understanding that alterations in mood and the regulation of mood seem to have a very important role in the initiation and maintenance of AN. We also were able to assess the response to AC stimulation in depression, given the presence of a large series of cases in our setting. Our initial work has been a phase I clinical trial to establish safety and tolerability: we are presently in the midst of a phase II trial to start the process of evaluating efficacy. Entry criteria for the trial includes a history of either chronic, treatment- resistant AN, or malignant AN. Risk of a premature death in the reasonably near future was an important factor to consider in selecting subjects suitable for the trial, which does represent a last hope for many subjects.
Our study presently has 15 subjects enrolled who have had the procedure. Six further patients are awaiting surgery. We recruited our first 12 patients in approximately 14 months. By comparison, in the first trial of DBS for depression conducted in this setting, it took two years to recruit the first 6 subjects. This alone suggests that there is a meaningful population of individuals with chronic, severe AN who are willing to undergo experimental neurosurgery in the hope that they might derive some benefit from the procedure.
We set a threshold of a BMI of 13 to be able to perform the surgery. Several subjects required hospitalizations before surgery to make them suitable for the procedure.
Our operative experience has been positive, with few adverse events, none of which were unexpected. Patients tolerated the procedure well, and there were few post-operative complications. One patient, with severe comorbid OCD did find it impossible to resist picking at the incision line in her scalp and we eventually had to remove the device.
Dr Woodside is Medical Director, Program for Eating Disorders, Toronto General Hospital, and Professor, Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada. Dr Lipsman is a resident in the Department of Neurosurgery, Toronto Western Hospital, Toronto, Ontario, Canada. Dr Lozano is Chair, Division of Neurosurgery, Toronto Western Hospital, and Professor, Department of Surgery, University of Toronto, Toronto, Ontario, Canada.
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2. Arcelus J, Mitchell AJ, Wales J, Nielsen S. Mortality rates in patients with anorexia nervosa and other eating disorders. A meta-analysis of 36 studies. Arch Gen Psychiatry. 2011l;68:724-731.
3. Lipsman N, Woodside B, Lozano AM. Evaluating the potential of deep brain stimulation for treatment-resistant anorexia nervosa. Handb Clin Neurol. 2013;116:271-276.
4. Lipsman N, Woodside DB, Lozano A. Deep Brain Stimulation in Anorexia Nervosa. Eating Disorders Research Society Annual Meeting [Poster presentation]. Bethesda, MD. September 2013.
5. Lipsman N, Woodside DB, Giacobbe P, et al. Subcallosal cingulate deep brain stimulation for treatment-refractory anorexia nervosa: a phase 1 pilot trial. Lancet. 2013;381:1361-1370.